Difference between revisions of "Acute myeloid leukemia, FLT3-positive"
Warner-admin (talk | contribs) |
(Added Gilteritinib) Tag: visualeditor-switched |
||
Line 30: | Line 30: | ||
===Regimen {{#subobject:c95c56|Variant=1}}=== | ===Regimen {{#subobject:c95c56|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] | ||
Line 63: | Line 63: | ||
===Regimen {{#subobject:b52969|Variant=1}}=== | ===Regimen {{#subobject:b52969|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] | ||
Line 95: | Line 95: | ||
===Regimen {{#subobject:b50325|Variant=1}}=== | ===Regimen {{#subobject:b50325|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] | ||
Line 152: | Line 152: | ||
===Variant #3 {{#subobject:c52466|Variant=1}}=== | ===Variant #3 {{#subobject:c52466|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[http://www.bloodjournal.org/content/105/1/54.long Stone et al. 2004] | |[http://www.bloodjournal.org/content/105/1/54.long Stone et al. 2004] | ||
Line 171: | Line 171: | ||
=Relapsed or refractory, further lines of therapy= | =Relapsed or refractory, further lines of therapy= | ||
+ | ==Gilteritinib monotherapy {{#subobject:0384e2|Regimen=1}}== | ||
+ | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
+ | |- | ||
+ | |[[#top|back to top]] | ||
+ | |} | ||
+ | ===Regimen {{#subobject:10f04d|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 50%" |Study | ||
+ | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !Comparator | ||
+ | |- | ||
+ | |ADMIRAL | ||
+ | | style="background-color:#91cf61" |Phase III | ||
+ | |Salvage Chemotherapy | ||
+ | |} | ||
+ | ====Chemotherapy==== | ||
+ | *[[Gilteritinib (ASP2215)|Gilteritinib (Xospata)]] 120 mg PO Daily | ||
+ | |||
+ | '''28-day cycle''' | ||
+ | |||
+ | ===References=== | ||
+ | # [https://clinicaltrials.gov/ct2/show/NCT02421939 Clinical Trial] | ||
==Azacitidine & Sorafenib {{#subobject:e3a8ee|Regimen=1}}== | ==Azacitidine & Sorafenib {{#subobject:e3a8ee|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
Line 179: | Line 201: | ||
===Regimen {{#subobject:9c1ff|Variant=1}}=== | ===Regimen {{#subobject:9c1ff|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ Ravandi et al. 2013] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ Ravandi et al. 2013] | ||
| style="background-color:#91cf61" |Phase II | | style="background-color:#91cf61" |Phase II | ||
|- | |- | ||
+ | | | ||
|} | |} | ||
====Chemotherapy==== | ====Chemotherapy==== |
Revision as of 19:55, 28 November 2018
Page editor | |
---|---|
Martin Schoen, MD, MPH St. Louis, MO |
Note: these are biomarker-specific regimens for patients with FLT3 internal tandem duplicated (FLT3-ITD) or tyrosine kinase domain mutated (FLT3-TKD) AML, please see the main AML page for other regimens.
22 regimens on this page
26 variants on this page
|
Upfront induction therapy, standard patients
7+3d & Midostaurin
Cytarabine, Daunorubicin, and Midostaurin induction therapy for acute myeloid leukemia (AML)
First-line induction therapy, older patients or "unfit" patients
7+3d & Sorafenib
back to top |
Regimen
Study | Evidence |
---|---|
Uy et al. 2017 (CALGB 11001) | Phase II |
Chemotherapy
- Cytarabine (Cytosar) 100 mg/m2/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
- Sorafenib (Nexavar) 400 mg PO BID on days 1 to 7
7-day course
Subsequent treatment
- Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 & sorafenib
- Patients achieving a CR or CRi: IDAC & sorafenib consolidation
References
- CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article contains verified protocol link to PMC article PubMed
Consolidation after upfront therapy
HiDAC & Midostaurin
Cytarabine & Midostaurin consolidation therapy for acute myeloid leukemia (AML)
IDAC & Sorafenib
back to top |
IDAC & Sorafenib: Intermediate Dose Ara-C (Cytarabine) & Sorafenib
Regimen
Study | Evidence |
---|---|
Uy et al. 2017 (CALGB 11001) | Phase II |
Preceding treatment
Chemotherapy
- Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours once per day on days 1 to 5
- Sorafenib (Nexavar) 400 mg PO BID for 28 days
Two cycles
Subsequent treatment
References
- CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article contains verified protocol link to PMC article PubMed
Maintenance after upfront therapy
Midostaurin monotherapy
Midostaurin (Rydapt) maintenance therapy for acute myeloid leukemia (AML)
Sorafenib monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Uy et al. 2017 (CALGB 11001) | Phase II |
Preceding treatment
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO BID
28-day cycle for up to 12 cycles
References
- CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article contains verified protocol link to PMC article PubMed
Relapsed or refractory, salvage therapy
Midostaurin monotherapy
back to top |
Variant #1
Study | Evidence | Comparator |
---|---|---|
Fischer et al. 2010 | Randomized Phase IIB (E) | Midostaurin 100 mg BID |
Chemotherapy
- Midostaurin (Rydapt) 50 mg PO BID
Continued indefinitely
Variant #2
Study | Evidence | Comparator |
---|---|---|
Fischer et al. 2010 | Randomized Phase IIB (E) | Midostaurin 50 mg BID |
Chemotherapy
- Midostaurin (Rydapt) 100 mg PO BID
Continued indefinitely
Variant #3
Study | Evidence |
---|---|
Stone et al. 2004 | Phase II |
Patients were required to have a FLT3 ITD or FLT3 p.D835Y mutation.
Chemotherapy
- Midostaurin (Rydapt) 75 mg PO TID
28-day cycles
References
- Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005 Jan 1;105(1):54-60. Epub 2004 Sep 2. link to original article contains verified protocol PubMed
- Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. Epub 2010 Aug 23. link to original article link to PMC article contains verified protocolPubMed
Relapsed or refractory, further lines of therapy
Gilteritinib monotherapy
back to top |
Regimen
Study | Evidence | Comparator |
---|---|---|
ADMIRAL | Phase III | Salvage Chemotherapy |
Chemotherapy
- Gilteritinib (Xospata) 120 mg PO Daily
28-day cycle
References
Azacitidine & Sorafenib
back to top |
Regimen
Study | Evidence |
---|---|
Ravandi et al. 2013 | Phase II |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 SC or IV once per day on days 1 to 7
- Sorafenib (Nexavar) 400 mg PO BID
Supportive medications
- "All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."
4 to 8 week cycles at treating physician's discretion
References
- Ravandi F, Alattar ML, Grunwald MR, Rudek MA, Rajkhowa T, Richie MA, Pierce S, Daver N, Garcia-Manero G, Faderl S, Nazha A, Konopleva M, Borthakur G, Burger J, Kadia T, Dellasala S, Andreeff M, Cortes J, Kantarjian H, Levis M. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013 Jun 6;121(23):4655-62. Epub 2013 Apr 23. link to original article contains verified protocol link to PMC article PubMed
Investigational agents
These are drugs under study with at least some promising results for this disease.